usp 800: beyond the basics part ii · pharmacy school, she joined memorial regional hospital...

USP 800: Beyond the BasicsPart II

Marie Louis-Jeune, PharmD, BCPSPharmacy Quality and Safety Coordinator

Memorial Cancer InstituteNovember 9, 2019

BibliographyMarie Louis-Jeune completed her undergraduate experience obtaining a Bachelor of Science in Exercise Science from Florida State University in 2009. Marie then went on to earn her Doctor of Pharmacy degree from South University School of Pharmacy in Savannah, Georgia in 2012. Following pharmacy school, she joined Memorial Regional Hospital completing a PGY-1 in Pharmacy Practice. Post residency, Marie transitioned into a Clinical Pharmacist role at Joe DiMaggio Children’s Hospital. During this time, she obtained her Board Certification in Pharmacotherapy and worked in various specialties including PICU and Hematology/Oncology. Marie then went on to complete a PGY-2 residency in Health-System Pharmacy Administration. During this time, she completed the ASHP Pharmacy Leadership Academy. She also served as the 2015-2016 Treasurer for the Florida Hospital Orlando Residency Program and was a 2015-2016 Communications and Awards Committee member of the Pharmacy Administration Resident Collaboration. Post residency, Marie transitioned into the Pharmacy Sterile Compounding Supervisor role at Memorial Cancer Institute in 2016. Her role evolved into the Pharmacy Operations Manager in 2017 and during this time she completed the ASHP Medication Safety Certificate. She is currently, since 2018, the Pharmacy Safety and Quality Coordinator. Marie is a member of FSHP and FLASCO.

Disclosure

I do not have any commercial interest, financial relationships, or conflicts of interest to disclose in regards to the content of this presentation.

Objectives

• Explain USP 800 recommendations on environmental sampling and medical surveillance

• Understand the key components of selecting a certification vendor• Discuss USP 800 recommendations, ASCO’s position and NIOSH future

goals on CSTDs• Review recommendations on evaluating CSTDs• Identify the financial impact of implementing and utilizing CSTDs

Abbreviations• ASCO: American Society of Clinical Oncology• CI: Confidence Interval• CSTD: Closed System Transfer Devices• GPO: Group Purchasing Organization• GRADE: Grading of Recommendations Assessment, Development and

Evaluation • HD: Hazardous Drug• MD: Mean Difference• NIOSH: National Institute for Occupational Safety and Health• ROBINS-I tool: risk of bias in non-randomised studies of interventions tool• RR: Risk Ratio• USP: United States Pharmacopeia

CSTD

USP 800 ASCO NIOSH

USP 800• CSTD: Supplemental engineering control

Recommendation

• CSTDs should be used when compounding HDs.

• CSTDs must be used when administering HDs.

• Carefully evaluate performance claims associated with available

CSTDs based on independent, peer-reviewed studies and

demonstrated containment reduction.

ASCOPosition Statement

• A testing protocol for CSTDs is needed.

• There is a need for a process to identify and certify effective CSTDs.

Qualifying statement

• CSTDs plus safe handling of HDs versus safe handling alone for

reducing exposure to infusional HDs in healthcare staff

CSTDs plus safe handling of HDs versus safe handling alone for reducing exposure to infusional HDs in healthcare staff

Objective

• Assess the effects of CSTD of infusional HD plus safe handling versus safe

handling alone for reducing staff exposure to infusional HDs and risk of staff

contamination.

Selection criteria

• Included comparative studies of any study design that compared CSTD plus

safe handling versus safe handling alone for infusional HDs.

– Irrespective of language, blinding, or publication status


Data collection and analysis

• Two review authors independently identified trials and extracted data.

• Calculated the RR) and MD with 95% CI using both fixed-effect and random-

effects models.

• Assessed risk of bias according to the ROBINS-I tool, used an intracluster

correlation coefficient of 0.10.

• Assessed the quality of the evidence using GRADE.


Main Results

• 23 observational cluster studies (358 hospitals)

• No randomized controlled trials identified

– Description of control groups were varied

– 21 studies: intervention and control used by pharmacist

and/or technician

– 2 studies: intervention and control used by nursing,

pharmacist or technicians

• 21 studies provided data on one or more outcomes

• CTSD used in the studies

– CSTD A (13 studies)

– CSTD B (1 study)

– CSTD C (1 study)

– CSTD A & B (1 study)

– Varied ( 5 studies)

– Not stated (2 studies)

Closed-system transfer device safe handling versus safe handling alone for reducing healthcare staff exposure to infusional hazardous drugs: exposure and contamination

Outcomes Illustrative comparative risks* (95%CI) Relative effects(95% CI)

Quality of the evidence (GRADE)Assumed risk Corresponding risk

Safe handling alone CSTD + safe handling

Exposure (urine tests for exposure)

Cyclophosphamidealone

917 per 1000 761 per 1000(422 to 1393)

RR 0.83(0.46 to 1.52)

Very low

Cyclophosphamide or ifosfamide

714 per 1000 64 per 1000(0 to 1000)

RR 0.09(0.00 to 2.79)

Very low

Cyclophosphamide, ifosfamide, or gemcitabine

There were no participants with exposure in either group.

Very low

Other measures of exposure

None of the studies report on blood tests or other measures of exposure to infusional hazardous drugs.



Quality of the evidence (GRADE)

Assumed risk Corresponding risk


Surface contamination (proportion of surfaces contaminated): Pharmacy areas

Cyclophosphamide,ifosfamide,

methotrexate, 5-fluorouracil, cytarabine,

gemcitabine

102-507 per 1000 90-451 per 1000 RR 0.65-0.96(include 1)

Very low

Irinotecan, docetaxel, paclitaxel,

vinorelbine, ganciclovir,

multiple drugs

There is no evidence of difference in the proportion of samples contaminated with drug in patient-care areas

between CSTD plus safe handling and safe handling alone.

Very low



Quality of the

evidence (GRADE)



Surface contamination (proportion of surfaces contaminated): Patient-care areas

Cyclophosphamide 440 per 1000 444 per 1000(378 to 519)

RR 1.01(0.86 to 1.18)

Very low

Ifosfamide 71 per 1000 102 per 1000(64 to 161)

RR 1.44(0.91 to 2.28)

Very low

Methotrexate 25 per 1000 25 per 1000(14 to 46)

RR 1.00(0.55 to 1.85)

Very low

5-fluorouracil, cytarabine,

gemcitabine, irinotecan, docetaxel,

paclitaxel, vinorelbine, multiple

drugs

There is no evidence of difference in the proportion of samples contaminated with drug in patient-care areas

between CSTD plus safe handling and safe handling alone.

Very low


Outcomes Illustrative comparative risks* (95%CI)

Relative effects(95% CI)

Quality of the

evidence (GRADE)



Surface contamination (quantity of surface contamination (pg/ cm²)): Pharmacy areas

Cyclophosphamide 124.30 pg/ cm²

49.34 pg/ cm²lower

MD −49.34 pg/ cm²(−84.11 to −14.56)

Very low

Ifosfamide 10.8 pg/ cm² 0.32 pg/ cm² lower MD −0.32 pg/ cm²(−6.58 to 5.94)

Very low

Methotrexate 18.23 pg/ cm² 3.09 pg/ cm² lower MD −3.09 pg/ cm²(−13.80 to 7.61)

Very low

5-fluorouracil 8720.5 pg/ cm²

257.87 pg/ cm² higher

MD 257.87(−459.65 to 975.38)

Very low

Cytarabine, gemcitabine, and

irinotecan

There is no evidence of difference in the amount of drug in pharmacy areas between CSTD plus safe handling

and safe handling alone.

Very low


Outcomes Illustrative comparative risks* (95%CI)

Relative effects(95% CI)

Quality of the

evidence (GRADE)


Safe handling alone

CSTD + safe handling

Surface contamination (quantity of surface contamination (pg/ cm²)): Patient-care areas

Cyclophosphamide 168 pg/ cm² 13.34 pg/ cm² lower

MD −13.34 pg/ cm²(−36.01 to 9.32)

Very low

Ifosfamide 4.59 pg/ cm² 3.59 pg/ cm² higher

MD 3.59 pg/ cm²(−3.45 to 10.63)

Very low

Methotrexate 1.42 pg/ cm² 0.10 pg/ cm² higher

MD 0.10 pg/ cm²(−0.57 to 0.78)

Very low

5-fluorouracil, cytarabine,

gemcitabine, and irinotecan

There is no evidence of difference in the amount of drug in patient-care areas between CSTD

plus safe handling and safe handling alone.

Very low

Other measures of contamination

None of the studies report on atmospheric contamination.

ASCOQualifying Statement

• Review of evidence for CSTDs did not find any published studies that

evaluated health outcomes but rather found studies of surrogate

markers

– Antineoplastic drugs in urine, surface contamination, and containment

levels of drugs in controlled laboratory settings

• Largely industry-sponsored body of evidence was of low quality.

• Need for third party to develop neutral testing method to determine

efficacy of CSTDs.

ASCOQualifying statement

• NIOSH in process of developing an independent vapor containment

performance protocol for CSTDs in health care settings.

• ASCO standards will be revised to incorporate the NIOSH CSTD

testing protocol when it becomes available.

• NIOSH encouraged to develop a certification process so that

practices can identify effective CSTDs.

NIOSHPerformance Test Protocol for CSTDs

• Collaborative effort between healthcare industry representatives

and NIOSH researchers.

• Healthcare industry request for independently developed

containment test protocol

• 2004 NIOSH Alert released while limited models of CSTDs in market

– Recent increase in CSTDs models in market


• Purpose is to challenge a CSTD’s ability to function as a closed

system that restricts drug mass (vapor or liquid) from crossing the

system boundary and escaping into the surrounding environment

– Not to demonstrate CSTDs are effective in reducing hazardous drug

surface contamination


• CSTD performance standards in regards to sterile practice for patient

protection exist.

• CSTD performance standards in regards to drug containment do not

exist.

• Consumers have no worker-protection performance basis to make

their selection of a CSTD.

• May be inclined to select a product based on acquisition costs and

uncertain claims of protective performance.


• Upon publication, manufacturers of CSTDs and consumers will be

able to use and refer to this protocol, enabling consumers to

conduct meaningful comparisons between products and

subsequently choose products based upon their demonstrated

ability to perform as closed systems.

Lessons Learned

NIOSH requires the use of CSTDs when transferring hazardous drugs from primary

packaging to infusion bags, bottles, or pumps.

True or False

CSTD

USP 800 ASCO NIOSH

Carefully evaluate performance claims.

A testing protocol and process to identify and certify effective CSTDsis needed. Standards will be revised to incorporate NIOSH protocol when it becomes available.

Performance test protocol for CSTDs to assist with product selection based upon ability to perform as closed systems.

Lessons Learned

NIOSH is in the process of developing an independent vapor containment performance protocol for CSTDs in health care settings and

the ASCO standards will be revised to incorporate these testing protocol once

available.

True or False

Financial Impact

Financial Impact

Contract Dependent

Primary or Secondary Wholesaler

Bulkiness of Product

NIOSH List Inclusion

CSTD Conversion

Agreement period

• Availability to extend the agreement period/term

Pricing• Supplier’s listed price

• Agreement period

• Instant rebate

• Sole Source Agreement

• Medicare and Medicaid Anti-Kickback statue

• Direct purchases from Supplier vs. Wholesaler

• Purchases from supplier requires additional payment for carrier and shipping

Contract Dependent

Customer’s utilization commitment

• Identifies percentage requirement of utilization for CSTD products

• Customer may be asked to provide proof of purchases for all similar products

during the applicable period

• At risk of increasing customers product pricing to tier level under customer’s

current GPO agreement

• Increase in price also affect by GPO membership

Contract Dependent

Wholesaler

Item Description Primary Wholesaler PriceSecondary Wholesaler PriceSavings/LossBag access port $90.00 $100.00 ($10.00)CSTD Male Leur $100.00 $120.00 ($20.00)Vial adapter A $1,600.00 $1,800.00 ($200.00)Vial adapter B $21,000.00 $24,000.00 ($3,000.00)Vial adapter C $1,500.00 $1,600.00 ($100.00)Secondary CSTD filtered line $4,500.00 $5,000.00 ($500.00)Secondary CSTD line $2,500.00 $4,000.00 ($1,500.00)CSTD spike adapter $250.00 $400.00 ($150.00)CSTD 10 mL syringe $1,600.00 $1,700.00 ($100.00)CSTD 20 mL syringe $2,400.00 $2,600.00 ($200.00)CSTD 30 mL syringe $2,000.00 $2,500.00 ($500.00)CSTD 3 mL syringe $2,000.00 $2,200.00 ($200.00)CSTD 5 mL syringe $4,000.00 $4,100.00 ($100.00)CSTD 60 mL syringe $1,900.00 $2,000.00 ($100.00)

TOTAL ($6,680.00)

Storage space

- Minimize ordering and PAR level

- Potential for drop shipment if inventory not managed appropriately

Request more frequent hazardous bin pick up or order more bins

- Identify amount of space in room held for pick up



VS


Current Practice

USP 800

Risk Assessment

December 2019


Antineoplastic drugs

Cytotoxic; Meet one or more NIOSH criteria for HDs; Additional reproductive toxicities to men and women; Occupational hazard to healthcare workers

Brentuximab, carboplatin, vinblastine

Non-antineoplastic drugs

Meet one or more NIOSH criteria for HDs; Some represent reproductive occupational hazard; Varying degrees of occupational exposure risk

Dexrazoxane, ganciclovir, phenytoin, tacrolimus

Non-antineoplastic drugs WITH reproductive effects

Primarily meet NIOSH criteria for reproductive hazards; Potential reproductive occupational hazard; Varying degrees of occupational exposure risk

Oxytocin, valproate, zonisamide

NIOSH 2016

Purchase CSTD Purchase Data

January - September 2019

ALPHABETIC ORDER

ITEM DESCRIPTION Hospital A Hospital B Hospital C Hospital D GRAND TOTAL ANNUALIZED

Bag access port $300.00 $50.00 $3,000.00 $30,000.00 $33,350.00 $44,466.67

CSTD Male Leur $20.00 $200.00 $4,000.00 $28,000.00 $32,220.00 $42,960.00

Vial adapter A $5,000.00 $26,000.00 $31,000.00 $41,333.33

Vial adapter B $200.00 $2,000.00 $6,000.00 $24,000.00 $32,200.00 $42,933.33

Vial adapter C $201.00 $2,001.00 $7,000.00 $22,000.00 $31,202.00 $41,602.67

Secondary CSTD filtered line $202.00 $2,002.00 $8,000.00 $20,000.00 $30,204.00 $40,272.00

Secondary CSTD line $9,000.00 $18,000.00 $27,000.00 $36,000.00

CSTD spike adapter $10,000.00 $16,000.00 $26,000.00 $34,666.67

CSTD 10 mL syringe $600.00 $11,000.00 $14,000.00 $25,600.00 $34,133.33

CSTD 20 mL syringe $400.00 $12,000.00 $12,000.00 $24,400.00 $32,533.33

CSTD 30 mL syringe $700.00 $13,000.00 $10,000.00 $23,700.00 $31,600.00

CSTD 3 mL syringe $300.00 $100.00 $14,000.00 $8,000.00 $22,400.00 $29,866.67

CSTD 5 mL syringe $15,000.00 $6,000.00 $21,000.00 $28,000.00

CSTD 60 mL syringe $16,000.00 $4,000.00 $20,000.00 $26,666.67

GRAND TOTAL $2,523.00 $6,753.00 $133,000.00 $238,000.00 $380,276.00 $507,034.67

CSTD Conversion

CSTD Conversion

Cost Quality

Quality of performance

Other contracts may be affected

Input from key players

Contract terms

Price

CSTD Conversion

Summary

• A testing protocol and process to identify and certify effective CSTDs is needed.

• Standards will be revised to incorporate NIOSH protocol when it becomes available.

• CSTD financial impact is multifactorial including the contract terms and NIOSH list of

inclusion.

• Quality may outweigh cost during CSTD implementation or conversion.

• Prior to implementation of the testing protocol, site specific evaluation should include

frontline staff and prior knowledge base of workflow issues with the CSTD in question.

1. USP Chapter <800> Hazardous Drugs – Handling in Healthcare Settings. United States Pharmacopeia 42-National Formulary 37.; 2019.

2. Celano P, et al. Safe Handling of Hazardous Drugs: ASCO Standards. J Clin Oncol 37:598-609, 2019.3. Gurusamy KS, Best LM, Tanguay C, et al: Closed-system drug-transfer devices plus safe handling of hazardous

drugs versus safe handling alone for reducing exposure to infusional hazardous drugs in healthcare staff. Cochrane Database Syst Rev 3:CD012860, 2018.

4. National Institute for Occupational Safety and Health: NIOSH Alert: Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. https://www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf. Accessed August 28, 2019.

5. National Institute for Occupational Safety and Health: A Performance Test Protocol for Closed System Transfer Devices Used During Pharmacy Compounding and Administration of Hazardous Drugs. https://www.cdc.gov/niosh/docket/review/docket288a/pdfs/APerformanceTestProtocolforClosedSystemTransferDevices.pdf. Accessed September 3, 2019.

6. Connor TH, MacKenzie BA, DeBord DG, Trout DB, O’Callaghan JP. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings, 2016. Cincinnati, OH: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Publication Number 2016-161.

7. Jacobson JO, Polovich M, McNiff KK, et al: American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards. J Clin Oncol 27: 5469-5475, 2009

References

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